Prioritizing of potential environmental exposure carcinogens beyond IARC group 1-2B based on weight of evidence (WoE) approach.

Environmental exposures are the main cause of cancer, and their carcinogenicity has not been fully evaluated, identifying potential carcinogens that have not been evaluated is critical for safety. This study is the first to propose a weight of evidence (WoE) approach based on computational methods to prioritize potential carcinogens. Computational methods such as read across, structural alert, (Quantitative) structure-activity relationship and chemical-disease association were evaluated and integrated. Four different WoE approach was evaluated, compared to the best single method, the WoE-1 approach gained 0.21 and 0.39 improvement in the area under the receiver operating characteristic curve (AUC) and Matthew's correlation coefficient (MCC) value, respectively. The evaluation of 681 environmental exposures beyond IARC list 1-2B prioritized 52 chemicals of high carcinogenic concern, of which 21 compounds were known carcinogens or suspected carcinogens, and eight compounds were identified as potential carcinogens for the first time. This study illustrated that the WoE approach can effectively complement different computational methods, and can be used to prioritize chemicals of carcinogenic concern.

Developmental neurotoxicity (DNT) QSAR combination prediction model establishment and structural characteristics interpretation.

With the incidence of neurodevelopmental disorders on the rise, it is imperative to screen and evaluate developmental neurotoxicity (DNT) compounds from a large number of environmental chemicals and understand their mechanisms. In this study, DNT qualitative structure-activity relationship (QSAR) study was carried out for the first time based on DNT data of mammals and structural characterization of DNT compounds was preliminarily illustrated. Five different classification algorithms and two feature selection methods were used to construct prediction models. The best model had good predictive ability on the external test set, but a small application domain (AD). Through combining of three different models, both MCC and AD values were improved. Furthermore, electronical properties, van der Waals volume-related properties and S, Cl or P containing substructure were found to be associated with DNT through modeling descriptors analysis and structure alerts (SAs) identification. This study lays a foundation for further DNT prediction of environmental exposures in human and contributes to the understanding of DNT mechanism.

Transcriptome analysis reveals the mechanism for blue-light-induced biosynthesis of delphinidin derivatives in harvested purple pepper fruit.

Anthocyanins are the main pigments that affect the color and quality of purple-fruited sweet pepper (Capsicum annuum). Our previous study indicated that blue light can induce anthocyanin accumulation in purple pepper. In view of its underlying mechanism that is unclear, here, anthocyanin content was determined, and transcriptome analysis was performed on pepper fruits harvested from different light treatments. As a result, among the identified anthocyanin metabolites, the levels of delphinidin (Dp) glycosides, including Dp-3-O-rhamnoside, Dp-3-O-rutinoside, and Dp-3-O-glucoside, were highly accumulated in blue-light-treated fruit, which are mainly responsible for the appearance color of purple pepper. Correlation between anthocyanin content and transcriptomic analysis indicated a total of 1,619 upregulated genes were found, of which six structural and 12 transcription factor (TF) genes were involved in the anthocyanin biosynthetic pathway. Structural gene, for instance, CaUFGT as well as TFs such as CaMYC2-like and CaERF113, which were highly expressed under blue light and presented similar expression patterns consistent with Dp glycoside accumulation, may be candidate genes for anthocyanin synthesis in response to blue-light signal.

Supplementation of Medium-Chain Triglycerides Combined with Docosahexaenoic Acid Inhibits Amyloid Beta Protein Deposition by Improving Brain Glucose Metabolism in APP/PS1 Mice.

The deterioration of brain glucose metabolism predates the clinical onset of Alzheimer's disease (AD). Medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively improve brain glucose metabolism and decrease the expression of AD-related proteins. However, the effects of the combined intervention are unclear. The present study explored the effects of the supplementation of MCTs combined with DHA in improving brain glucose metabolism and decreasing AD-related protein expression levels in APP/PS1 mice. The mice were assigned into four dietary treatment groups: the control group, MCTs group, DHA group, and MCTs + DHA group. The corresponding diet of the respective groups was fed to mice from the age of 3 to 11 months. The results showed that the supplementation of MCTs combined with DHA could increase serum octanoic acid (C8:0), decanoic acid (C10:0), DHA, and ß-hydroxybutyrate (ß-HB) levels; improve glucose metabolism; and reduce nerve cell apoptosis in the brain. Moreover, it also aided with decreasing the expression levels of amyloid beta protein (Aß), amyloid precursor protein (APP), ß-site APP cleaving enzyme-1 (BACE1), and presenilin-1 (PS1) in the brain. Furthermore, the supplementation of MCTs + DHA was significantly more beneficial than that of MCTs or DHA alone. In conclusion, the supplementation of MCTs combined with DHA could improve energy metabolism in the brain of APP/PS1 mice, thus decreasing nerve cell apoptosis and inhibiting the expression of Aß.

The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats.

Progressive bone marrow (BM) fat accumulation is a common bone loss characteristic in older populations and glucocorticoid (GC)-induced skeletal destruction that is inversely associated with bone synthesis and directly associated with increased peroxisomal proliferator-activated receptor gamma (PPARγ) expression. PPARγ inhibition is an efficient therapeutic strategy for aged- and GC-related skeletal disorders. This study aimed to evaluate the effect of PPARγ inhibition on aged GC-treated female rats. It was hypothesised that bisphenol A diglycidyl ether (BADGE) could inhibit marrow adiposity and improve osteogenesis by inhibiting PPARγ, thereby preventing GC-induced osteoporosis (GIO). Female Sprague-Dawley rats (n = 32, age = 18 months) were randomly allocated to one of the following groups: (1) control, (2) BADGE (30 mg/kg/day, intraperitoneal), (3) methylprednisolone (MP; 30 mg/kg/day, subcutaneous), and (4) MP + BADGE. After eight weeks of treatment, bone density (BD) and trabecular bone microarchitectures were quantified by micro-computed tomography (CT), and BM adipocytes were quantified by histopathology. Additionally, mRNA and protein expression of adipogenic and osteogenic markers were quantified by reverse transcription-quantitative polymerase chain reaction. Furthermore, serum bone turnover biomarker levels were quantified by enzyme-linked immunosorbent assay. MP treatment led to marrow adipogenesis and bone deterioration. However, rats treated with MP + BADGE showed lower marrow adipogenesis, as indicated by smaller marrow adipocyte diameter, decreased density and area percentages, reduced expression of marrow adipogenic genes and proteins, improved BD and trabecular microarchitectures, increased expression of osteogenic genes and proteins, and higher levels of serum bone formation markers. These results were consistent with the differences observed between control and BADGE mono-treated rats. In conclusion, BADGE treatment attenuates BM adiposity and improves bone formation in aged GC-treated female rats by inhibiting PPARγ. Therefore, PPARγ might be a potential target for treating GIO in older populations.

Long-term dietary folic acid supplementation attenuated aging-induced hippocampus atrophy and promoted glucose uptake in 25-month-old rats with cognitive decline.

The brain has high energy demand making it sensitive to changes in energy fuel supply. Aging shrinks brain volume, decreases glucose uptake availability of the brain, and finally, causes cognitive dysfunction. Folic acid supplementation delayed cognitive decline and neurodegeneration. However, whether folic acid affects brain energy metabolism and structural changes is unclear. The study aimed to determine if long-term dietary folic acid supplementation could alleviate age-related cognitive decline by attenuating hippocampus atrophy and promoting brain glucose uptake in Sprague-Dawley (SD) rats. According to folic acid levels in diet, 3-months old male SD rats were randomly divided into four intervention groups for 22 months in equal numbers: folic acid-deficient diet (FA-D) group, folic acid-normal diet (FA-N) group, low folic acid-supplemented diet (FA-L) group, and high folic acid-supplemented diet (FA-H) group. The results showed that serum folate concentrations decreased and serum homocysteine (Hcy) concentrations increased with age, and dietary folic acid supplementation increased serum folate concentrations and decreased Hcy concentrations at 11, 18, and 22 months of intervention. Dietary folic acid supplementation attenuated aging-induced hippocampus atrophy, which was showed by higher fractional anisotropy and lower mean diffusivity in the hippocampus, increased brain 18F-Fluorodeoxyglucose (18F-FDG) uptake, then stimulated neuronal survival, and alleviated age-related cognitive decline in SD rats. In conclusion, long-term dietary folic acid supplementation alleviated age-related cognitive decline by attenuating hippocampus atrophy and promoting brain glucose uptake in SD rats.

Mechanism of [CO2] Enrichment Alleviated Drought Stress in the Roots of Cucumber Seedlings Revealed via Proteomic and Biochemical Analysis.

Cucumber is one of the most widely cultivated greenhouse vegetables, and its quality and yield are threatened by drought stress. Studies have shown that carbon dioxide concentration ([CO2]) enrichment can alleviate drought stress in cucumber seedlings; however the mechanism of this [CO2] enrichment effect on root drought stress is not clear. In this study, the effects of different drought stresses (simulated with 0, 5% and 10% PEG 6000, i.e., no, moderate, and severe drought stress) and [CO2] (400 µmol·mol-1 and 800 ± 40 µmol·mol-1) on the cucumber seedling root proteome were analyzed using the tandem mass tag (TMT) quantitative proteomics method. The results showed that after [CO2] enrichment, 346 differentially accumulating proteins (DAPs) were found only under moderate drought stress, 27 DAPs only under severe drought stress, and 34 DAPs under both moderate and severe drought stress. [CO2] enrichment promoted energy metabolism, amino acid metabolism, and secondary metabolism, induced the expression of proteins related to root cell wall and cytoskeleton metabolism, effectively maintained the balance of protein processing and degradation, and enhanced the cell wall regulation ability. However, the extent to which [CO2] enrichment alleviated drought stress in cucumber seedling roots was limited under severe drought stress, which may be due to excessive damage to the seedlings.

Changes in rhizospheric microbiome structure and soil metabolic function in response to continuous cucumber cultivation.

With the increasing reliance on intensive arable agriculture, analysis of the problems associated with continuous cropping has become a global research focus. Here, high-throughput sequencing and nontargeted metabolomics were used to evaluate the responses of soil microbial community structure and soil metabolic function to continuous cucumber cultivation (from 1 to 18 years of continuous cultivation) in greenhouses. Continuous cucumber cropping resulted in increased soil nutrient concentrations, but decreased concentrations of available nutrients. The abundance of several bacterial genera associated with nutrient cycling, such as Bacillus and Sphingomonas, was reduced by continuous cucumber cultivation. The abundance of several beneficial fungal genera, including pathogen antagonists (e.g. Chaetomium, Mortierella, Aspergillus, and Penicillium), were found to gradually decrease in response to the increased duration of continuous cropping. 3-amino-2-naphthoic acid and L-valine increased initially and then decreased as the cropping continued, which were related to fatty acid metabolism and amino acid biosynthesis. We also confirmed a close association between microbial community structure and soil metabolites. This study linked the changes in microbial community structure and metabolites in the rhizosphere soil and provided new insights into soil-microbial interactions in continuous cucumber culture systems.

Nicotine Activating α4ß2 Nicotinic Acetylcholine Receptors to Suppress Neuroinflammation via JAK2-STAT3 Signaling Pathway in Ischemic Rats and Inflammatory Cells.

Nicotine plays a role in inhibiting inflammatory factors, which contributes to improving cognitive impairment by activating α4ß2 nAChRs in ischemic rats, but the underlying mechanism has not been fully elucidated. Janus tyrosine kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) signaling pathway is involved in cognitive improvement, and there seems to be a relationship between nAChRs and JAK2-STAT3 as well. The aim of this study is to explore the role of JAK2-STAT3 signaling pathway in nicotine-mediated anti-inflammatory effect. Nicotine, DHßE (the strongest competitive antagonist of α4ß2 nAChRs), and AG490 (a specific JAK2-STAT3 blocker) were used to intervene and treat ischemic rats and HEK-293 T-hα4ß2 cells. The Morris water maze (MWM) test and 2-[18F]-A-85380 PET imaging were performed to detect the cognitive function and α4ß2 nAChRs density in ischemic rats. The results demonstrated that nicotine intervention increased the density of α4ß2 nAChRs and improved cognitive impairment, but this effect was blocked by AG490, and the receptors were still upregulated. Essentially, when the JAK2-STAT3 signaling pathway was blocked, nicotine could only upregulate the expression of α4ß2 nAChRs, but not improve the cognitive function. PCR and Western blot analysis further confirmed these results. The cell experiments also showed that nicotine could reduce inflammatory factors stimulated by LPS and upregulate the expression of pJAK2 and pSTAT3 in HEK-293 T-hα4ß2 cells, while AG490 and DHßE reversed the effect of nicotine. To sum up, our work indicated that JAK2-STAT3 signaling pathway played an important role in nicotine-induced cognitive improvement by upregulating α4ß2 nAChRs in ischemic rats.

Overexpression of Foxc1 ameliorates sepsis­associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF­κB pathway.

Sepsis­associated encephalopathy (SAE) is a common and severe complication of sepsis. The cognitive dysfunction that ensues during SAE has been reported to be caused by impairments of the hippocampus. Microglia serves a key role in neuroinflammation during SAE through migration. Forkhead box C1 (Foxc1) is a member of the forkhead transcription factor family that has been found to regulate in cell migration. However, the role of Foxc1 in neuroinflammation during SAE remains unknown. In the present study, the mechanistic role of Foxc1 on microglial migration, neuroinflammation and neuronal apoptosis during the occurrence of cognitive dysfunction in SAE was investigated. A microglia­mediated inflammation model was induced by LPS in BV­2 microglial cells in vitro, whilst a SAE­related cognitive impairment model was established in mice using cecal ligation and perforation (CLP) surgery. Cognitive function in mice was evaluated using the Morris Water Maze (MWM) trial. Lipopolysaccharide (LPS) treatment was found to trigger BV­2 cell migration, inflammation and neuronal apoptosis. In addition, CLP surgery induced cognitive injury, which was indicated by longer latencies and shorter dwell times in the goal quadrant compared with those in the Sham group in the MWM trial. LPS treatment or CLP induction decreased the expression of Foxc1 and inhibitor of NF­κB (IκΒα) whilst increasing that of p65, IL­1ß and TNF­α. After Foxc1 was overexpressed, the cognitive dysfunction of mice that underwent CLP surgery was improved, with the expression of IκBα also increased, microglial cell migration, the expression of p65, IL­1ß and TNF­α and neuronal apoptosis were all decreased in vivo and in vitro, which were in turn reversed by the inhibition of IκBα in vitro. Overall, these results suggest that the overexpression of Foxc1 inhibited microglial migration whilst suppressing the inflammatory response and neuronal apoptosis by regulating the IκBα/NF­κB pathway, thereby improving cognitive dysfunction during SAE.

Visualization and validation of twin nucleation and early-stage growth in magnesium.

The abrupt occurrence of twinning when Mg is deformed leads to a highly anisotropic response, making it too unreliable for structural use and too unpredictable for observation. Here, we describe an in-situ transmission electron microscopy experiment on Mg crystals with strategically designed geometries for visualization of a long-proposed but unverified twinning mechanism. Combining with atomistic simulations and topological analysis, we conclude that twin nucleation occurs through a pure-shuffle mechanism that requires prismatic-basal transformations. Also, we verified a crystal geometry dependent twin growth mechanism, that is the early-stage growth associated with instability of plasticity flow, which can be dominated either by slower movement of prismatic-basal boundary steps, or by faster glide-shuffle along the twinning plane. The fundamental understanding of twinning provides a pathway to understand deformation from a scientific standpoint and the microstructure design principles to engineer metals with enhanced behavior from a technological standpoint.

Folic Acid Inhibits Aging-Induced Telomere Attrition and Apoptosis in Astrocytes In Vivo and In Vitro.

Folic acid (FA) has been reported to inhibit astrocyte apoptosis and improve aging-induced disorders; however, its role in telomere attrition remains unclear. In present study, 4-month-old senescence-accelerated mouse prone 8 (SAMP8) mice were assigned to four treatment groups for the in vivo experiment: FA-deficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group, and high FA-supplemented diet (FA-H) group. These mice were euthanized when 10 months old. There was also a young SAMP8 (4 months old) control group (Con-Y) fed with FA-normal diet. In in vitro study, primary cultures of astrocytes from hippocampus and cerebral cortex were incubated for five generations with various concentrations of FA (0-40 µM) and were assigned to five groups: FA 0 µM (generation 5), FA 10 µM (generation 5), FA 20 µM (generation 5), FA 40 µM (generation 5), and FA 10 µM (generation 1). The results showed that FA supplementation inhibited aging-induced astrocytosis, astrocyte apoptosis, neurodegeneration, and prevented telomere attrition in hippocampus and cortex of SAMP8 mice. FA supplementation also decreased apoptosis and telomere attrition, and increased telomerase activity, in primary cultures of astrocytes. These results showed that it may be one of the mechanisms that FA inhibiting aging-induced apoptosis of astrocyte by alleviating telomere attrition.

Physiological and Transcriptomic Analyses Revealed the Implications of Abscisic Acid in Mediating the Rate-Limiting Step for Photosynthetic Carbon Dioxide Utilisation in Response to Vapour Pressure Deficit in Solanum Lycopersicum (Tomato).

The atmospheric vapour pressure deficit (VPD) has been demonstrated to be a significant environmental factor inducing plant water stress and affecting plant photosynthetic productivity. Despite this, the rate-limiting step for photosynthesis under varying VPD is still unclear. In the present study, tomato plants were cultivated under two contrasting VPD levels: high VPD (3-5 kPa) and low VPD (0.5-1.5 kPa). The effect of long-term acclimation on the short-term rapid VPD response was examined across VPD ranging from 0.5 to 4.5 kPa. Quantitative photosynthetic limitation analysis across the VPD range was performed by combining gas exchange and chlorophyll fluorescence. The potential role of abscisic acid (ABA) in mediating photosynthetic carbon dioxide (CO2) uptake across a series of VPD was evaluated by physiological and transcriptomic analyses. The rate-limiting step for photosynthetic CO2 utilisation varied with VPD elevation in tomato plants. Under low VPD conditions, stomatal and mesophyll conductance was sufficiently high for CO2 transport. With VPD elevation, plant water stress was gradually pronounced and triggered rapid ABA biosynthesis. The contribution of stomatal and mesophyll limitation to photosynthesis gradually increased with an increase in the VPD. Consequently, the low CO2 availability inside chloroplasts substantially constrained photosynthesis under high VPD conditions. The foliar ABA content was negatively correlated with stomatal and mesophyll conductance for CO2 diffusion. Transcriptomic and physiological analyses revealed that ABA was potentially involved in mediating water transport and photosynthetic CO2 uptake in response to VPD variation. The present study provided new insights into the underlying mechanism of photosynthetic depression under high VPD stress.

Rational design of an HClO-specific triggered self-immolative fluorescent turn-on sensor and its bioimaging applications.

The development of a rapid and intuitive method for the detection of a specific small molecule biomarker is important for understanding the pathogenesis of relevant diseases. Described here is the design and evaluation of an HClO-specific triggered self-immolative fluorescent sensor (RESClO) based on the structure of an N-protected Resorufin dye. Due to the interrupted π-conjugated structure of the Resorufin dye, the free sensor showed very weak absorption and fluorescence. It can quickly complete the response to HClO (within 10 s) with high selectivity and sensitivity (LOD = 16.8 nM) in aqueous solution. The sensor can be made into test strips to quickly detect HClO in the environment by obvious changes in color and fluorescence. It was successfully used for bioimaging of exogenous and endogenous HClO in cells and zebra fish. More importantly, it can also be used for visual imaging of mouse arthritis models. Thus, sensor RESClO can provide a simple and promising visual analytical tool for the detection of HClO in the environment and the early diagnosis of HClO-mediated related diseases.

Antihyperlipidemic and Hepatoprotective Properties of Vitamin B6 Supplementation in Rats with High-Fat Diet-Induced Hyperlipidemia.

BACKGROUND: The incidence and mortality of hyperlipidemia are increasing year by year, showing a younger trend. At present, the treatment of hyperlipidemia is mainly dependent on western medicine, but its side effects on liver and kidney function are common in clinics. Therefore, it is necessary to study the treatment of hyperlipidemia by augmenting effective dietary nutrition supplements. Vitamin B6 (VitB6), as an essential cofactor for enzymes, participates in lipid metabolism. The effects of VitB6 on hyperlipidemia, however, have not been reported until now. AIM: The present study was to investigate the influence of VitB6 on hepatic lipid metabolism in hyperlipidaemia rats induced by a High-Fat Diet (HFD). METHODS: Male Sprague-Dawley rats were kept on HFD for two weeks to establish the hyperlipidemia model. The rats in low-dosage and high-dosage groups were received 2.00 and 3.00 mg/kg/- day of VitB6 for eight weeks, respectively. RESULTS: The results showed that both doses of VitB6 reduced HFD-induced hepatic Low-Density Lipoprotein Cholesterol (LDL-C); decreased blood cholesterol (TC), triglycerides, LDL-C, atherogenic index (AI), Atherogenic Index of Plasma (AIP), apolipoprotein B (ApoB) and ApoB/apolipoprotein A-1(ApoA1) ratio; increased liver High-Density Lipoprotein Cholesterol (HDL-C) and serum ApoA1; reduced hepatic steatosis and triglyceride accumulation, lowered fat storage, and recovered heart/body and brain/body ratio to a normal level. In addition, VitB6 supplementation markedly decreased HMGR level, increased the mRNA abundance of LDLR and CYP7A1, and protein expression of SIRT1, following the downregulation of SREBP-1 and PPARγ protein expression in the liver of hyperlipidemia rats. CONCLUSION: In summary, oral VitB6 supplementation can ameliorate HFD-induced hepatic lipid accumulation and dyslipidemia in SD rats by inhibiting fatty acid and cholesterol synthesis, promoting fatty acid decomposition and cholesterol transport.

CO2 enrichment enhanced drought resistance by regulating growth, hydraulic conductivity and phytohormone contents in the root of cucumber seedlings.

The coordinated effects of CO2 enrichment and drought stress on cucumber leaves have attracted increasing research attention, but few studies have investigated the effects of CO2 enrichment on the root system under drought stress. So we analyzed the morphological parameters, hydraulic conductivity, aquaporin-related gene expression, and endogenous phytohormone contents in roots of cucumber seedlings cultured under different CO2 concentrations (approximately 400 and 800 ± 40 µmol mol-1) and drought stresses simulated by polyethylene glycol 6000 (0%, 5%, and 10%). The results showed that under drought stress, regardless of the CO2 concentration, the root biomass and hydraulic conductivity decreased, the contents of auxin (IAA), zeatin nucleoside (ZR), and gibberellin (GA) decreased, the abscisic acid (ABA) content and the transcript levels of the aquaporin-related genes CsPIP2-4 increased, and the transcript levels of the aquaporin-related genes CsPIP2-5 and CsPIP2-7 decreased compared with no drought stress. Under moderate drought stress, CO2 enrichment decreased ABA content and the transcript level of CsPIP2-4, increased root biomass and GA content and the transcript level of CsPIP2-7, improved contribution rate of cell-to-cell water transport (mediated by aquaporins) and roots hydraulic conductivity. In summary, drought stress changed the water transport capacity of the roots and inhibited the growth of cucumber seedlings. CO2 enrichment regulated phytohormone contents and aquaporin-related gene expression, maintained the normal contribution rate of cell-to-cell water transport, and improved the root biomass and hydraulic conductivity, thereby alleviated the negative effects of drought stress on cucumber seedlings.

Intracranial Pressure Monitoring-Aided Management Associated with Favorable Outcomes in Patients with Hypertension-Related Spontaneous Intracerebral Hemorrhage.

To investigate the effect of intracranial pressure (ICP) monitoring on the functional outcome of patients with hypertension-related spontaneous intracerebral hemorrhage (ICH). We included 196 patients with Glasgow Coma Scale (GCS) scores of 3-12 in this observational study, of which 103 underwent ICP monitors. Binary and ordinal regression analyses were used to estimate the effect of ICP monitoring on the functional outcome. The rate of adverse events, blood pressure control, and length of hospitalization were compared between the two groups. ICP monitoring had a significant impact on the clinical outcome of patients by shifting the Extended Glasgow Outcome Scale (GOS-E) scores in a favorable direction (p = 0.027) and reducing mortality at discharge (p = 0.004) and 6 months later (p = 0.02). The rate of favorable outcome at 6 months was higher in the ICP-monitored group (p = 0.03). However, subgroup analysis showed that no relationship between ICP monitoring and clinical outcome was found for patients with GCS scores of 3-8. For patients with GCS scores of 9-12, the distribution of GOS-E scores at 6 months shifted in a favorable direction in the ICP-monitored group (p = 0.001). The rate of favorable outcome at 6 months was higher in the ICP-monitored group (p = 0.01). The mortality at discharge and 6 months later was also lower in the ICP-monitored group. Thus, our study supports the value of ICP monitoring in hypertension-related ICH patients with GCS scores of 3-12, especially those with GCS scores of 9-12.

Nicotine Induced Neurocognitive Protection and Anti-inflammation Effect by Activating α 4ß 2 Nicotinic Acetylcholine Receptors in Ischemic Rats.

INTRODUCTION: The main objective of this study was to explore the mechanism of nicotine improving cognitive impairments in ischemic rats. METHODS: Twenty adult male Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four different groups with different intervention: nicotine (1.5 mg/kg/d), dihydro-ß-erythroidine (DHßE; 3 mg/kg/d), nicotine (1.5 mg/kg/d) + DHßE (3 mg/kg/d), or saline, after ischemic model surgery. Another five male SD rats also underwent same surgery, while not injecting endothelin-1 but saline, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. All the rats underwent the MWM test, micro positron emission tomography imaging with 2-[18F]-A-85380, and messenger RNA (mRNA) test of α 4 nicotinic acetylcholine receptor (nAChR), ß 2 nAChR, tumor necrosis factor-alpha (TNF-α), IL-1ß, and IL-6. RESULTS: The MWM test showed the rats given nicotine showing better memory than ischemic rats (p < .05), whereas the rats given DHßE or both nicotine and DHßE did not show any statistical difference from the ischemic rats (p > .05). Micro positron emission tomography imaging showed higher uptake of tracer in the left thalamus and whole brain in rats given nicotine than in ischemic rats, but the rats given DHßE or both nicotine and DHßE did not. By real-time PCR test, the mRNA of α 4 nAChR and ß 2 nAChR in rats given nicotine increased significantly compared with ischemic rats and decreased TNF-α, IL-1ß, and IL-6 mRNA (all ps < .05). CONCLUSIONS: By activating α 4ß 2 nAChRs, nicotine plays a role in inhibiting the inflammatory factors, which contributes to improving cognitive impairment in ischemic rats. IMPLICATIONS: It is well acknowledged that vascular cognitive impairment (VCI) is the second most common cause of dementia after Alzheimer's disease. Cholinergic agents have potential for the symptomatic treatment of the cognitive symptoms of dementia, but the exact mechanism still remains unclear. There are potential complex associations and interactions between VCI and inflammation. This study showed that nicotine had anti-inflammatory potency, which is most likely because of the activation of the nAChRs. By activating α4ß2 nAChRs, nicotine played a role in inhibiting the inflammatory factors, which contribute to improving cognitive impairment in ischemic rats.

Physiological and iTRAQ based proteomics analyses reveal the mechanism of elevated CO2 concentration alleviating drought stress in cucumber (Cucumis sativus L.) seedlings.

Carbon dioxide is one of the most important anthropogenic greenhouse gases. We previously confirmed that elevated [CO2] alleviated the negative consequences of drought stress to cucumber seedlings, but the physiological mechanism remains unknown. We investigated the morphological and physiological characteristics as well as iTRAQ-based proteomics analyses in this study under different combinations [CO2] (400 and (800 ±â€¯20) µmol·mol-1) and water conditions (no, moderate and severe drought stress simulated by polyethylene glycol 6000). The results showed: (1) elevated [CO2] significantly increased plant height, stem diameter, leaf area and relative water content (RWC) under drought stress; (2) drought stress significantly increased J and K peaks of the chlorophyll a fluorescence transient, indicating the damage of photosynthetic electron transport chain, while elevated [CO2] decreased them especially under moderate drought condition; (3) iTRAQ-based proteomics analyses indicated that elevated [CO2] increased the abundance of psbJ and the PSI reaction center subunit VI-2 in seedlings exposed to moderate drought stress; (4) the abundance of uroporphyrinogen decarboxylase 2 and tetrapyrrole-binding protein decreased in response to elevated [CO2] under severe drought condition; (5) elevated [CO2] regulated the expression of chloroplast proteins such as those related to stress and defense response, redox homeostasis, metabolic pathways. In conclusion, elevated [CO2] enhanced the efficiency of photosynthetic electron transport, limited the absorption of excess light energy, enhanced the ability of antioxidant and osmotic adjustment, and alleviated the accumulation of toxic substances under drought stress. These findings provide new clues for understanding the molecular basis of elevated [CO2] alleviated plant drought stress.

Coordination between vapor pressure deficit and CO2 on the regulation of photosynthesis and productivity in greenhouse tomato production.

The high vapor pressure deficit (VPD) in some arid and semi-arid climates creates undesirable conditions for the growth of tomato plants (Solanum lycopersicum L., cv. Jinpeng). The global CO2 concentration ([CO2]) has also risen in recent years to levels above 400 µmol·mol-1. However, the coordinated effect of VPD and [CO2] on tomato plant growth remains unclear, especially at VPDs of 5-6 kPa or even higher that are extremely detrimental to plant growth. Here, we explore the interaction of VPD and [CO2] on plant water status, stomatal characteristics, and gas exchange parameters in summer greenhouses in a semi-arid area. Plants were grown in four adjacent glass greenhouses with different environmental conditions: (i) high VPD + low [CO2] representing natural/control conditions; (ii) high VPD + high [CO2] representing enriched CO2; (iii) low VPD + low [CO2] representing reduced VPD; and (iv) low VPD + high [CO2] representing reduced VPD and enriched CO2. Reducing the VPD alleviated the water stress of the plant and increased the gas exchange area of the leaf, which was beneficial to the entry of CO2 into the leaf. At this time, the increase of [CO2] was more beneficial to promote the photosynthetic rate and then improve the water use efficiency and yield.